The presence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in oceanic ecosystems constitutes an emerging public health risks in the marine environment. In this study, we report for the first time the identification of ESBL (CTX-M)-producing E. coli in wild fishes from a polluted area in the South Atlantic coast of Brazil, where a genomic analysis confirm the presence of livestock and human E. coli lineages belonging to sequence types (STs) ST744 and ST746, which carried clinically relevant resistance genes for human and veterinary antibiotics, and heavy metals. These findings reveal the presence of multidrug-resistant (MDR) bacteria in the gut microbiota of wild fishes living in polluted coastal waters, alerting that microbial contamination by bacteria related directly and indirectly to human or animal activities could affect the safety of the seafood supply, as well as the commercial and recreational use of coastal marine waters. •Occurrence of MDR bacteria in the Atlantic Coast of Brazil has been investigated.•Presence of ESBL (CTX-M)-producing E. coli in wild fishes is highlighted.•Genomic analysis revealed livestock and human E. coli lineages ST744 and ST746.•Dissemination of MDR pathogens in polluted marine ecosystems has been discussed.